Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression.

Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice. Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.

Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.

A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs.

Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2-/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2+ macrophages and a cellular response orchestrated by these cells. CCR2-/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2-/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV.

siRNA lipid nanoparticles for CXCL12 silencing modulate brain immune response during Zika infection.

CXCL12 is a key chemokine implicated in neuroinflammation, particularly during Zika virus (ZIKV) infection. Specifically, CXCL12 is upregulated in circulating cells of ZIKV infected patients. Here, we developed a lipid nanoparticle (LNP) to deliver siRNA in vivo to assess the impact of CXCL12 silencing in the context of ZIKV infection. The biodistribution of the LNP was assessed in vivo after intravenous injection using fluorescently tagged siRNA. Next, we investigated the ability of the developed LNP to silence CXCL12 in vivo and assessed the resulting effects in a murine model of ZIKV infection. The LNP encapsulating siRNA significantly inhibited CXCL12 levels in the spleen and induced microglial activation in the brain during ZIKV infection. This activation was evidenced by the enhanced expression of iNOS, TNF-α, and CD206 within microglial cells. Moreover, T cell subsets exhibited reduced secretion of IFN-É£ and IL-17 following LNP treatment. Despite no observable alteration in viral load, CXCL12 silencing led to a significant reduction in type-I interferon production compared to both ZIKV-infected and uninfected groups. Furthermore, we found grip strength deficits in the group treated with siRNA-LNP compared to the other groups. Our data suggest a correlation between the upregulated pro-inflammatory cytokines and the observed decrease in strength. Collectively, our results provide evidence that CXCL12 silencing exerts a regulatory influence on the immune response in the brain during ZIKV infection. In addition, the modulation of T-cell activation following CXCL12 silencing provides valuable insights into potential protective mechanisms against ZIKV, offering novel perspectives for combating this infection.

Delivery of Plasmid DNA by Ionizable Lipid Nanoparticles to Induce CAR Expression in T Cells.

Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR. Methods: Here, we formulated a mini-library of LNPs to deliver pDNA to T cells by varying the molar ratios of excipient lipids in each formulation. LNPs were characterized and screened in vitro using a T cell line (Jurkat). The optimized formulation was used ex vivo to engineer T cells derived from human peripheral blood mononuclear cells (PBMCs) for the expression of an anti-CD19 CAR (CAR-CD19BBz). The effectiveness of these CAR T cells was assessed in vitro against Raji (CD19+) cells. Results: LNPs formulated with different molar ratios of excipient lipids efficiently delivered pDNA to Jurkat cells with low cytotoxicity compared to conventional transfection methods, such as electroporation and lipofectamine. We show that CAR-CD19BBz expression in T cells was transient after transfection with LNPs. Jurkat cells transfected with our top-performing LNPs underwent activation when exposed to CD19+ target cells. Using our top-performing LNP-9-CAR, we were able to engineer human primary T cells to express CAR-CD19BBz, which elicited significant specific killing of CD19+ target cells in vitro. Conclusion: Collectively, our results show that LNP-mediated delivery of pDNA is a suitable method to engineer human T cells to express CAR, which holds promise for improving the production methods and broader application of this therapy in the future.

Depression and loneliness symptoms in Brazilian older people during the COVID-19 pandemic: a network approach.

OBJECTIVES: Depression and loneliness in older people were a global challenge during the COVID-19 pandemic. Causal mechanisms to trigger depression might vary across different life events. We aimed to apply network analysis in a sample of Brazilian older people during the first wave of the COVID-19 pandemic, to investigate if loneliness and depression symptoms were connected within a psychological network. We explored how symptoms manifested and interacted, to discuss possible interventions that could mitigate late-life depression and loneliness symptoms in face of the COVID-19 pandemic. METHOD: We collected data from 384 Brazilian older people who answered an online protocol to assess sociodemographic data, loneliness symptoms (assessed by the short version of UCLA-BR), and depression symptoms (assessed by the PHQ-2). RESULTS: 'Lack of companionship' was the bridge symptom connecting loneliness and depression communities. 'I feel shut out and excluded by others' and 'People are around me, but not with me' were the most predictable symptoms of loneliness. CONCLUSION: Interventions aimed to promote older people's social participation and skills, combined with strategies to expand their sources of social support and combat ageism, might be relevant to mitigate symptoms of loneliness and depression in older people during a crisis like the COVID-19 pandemic.

Implementação da Rede de Cuidados à Pessoa com Deficiência: na periferia da governança de São Paulo / Implementation of the Care Network for People with Disabilities: in the periphery of the São Paulo, Brazil, governance

Resumo A Rede de Cuidado à Pessoa com Deficiência (RCPD) foi implementada no Sistema Único de Saúde (SUS) para expandir o acesso aos serviços às pessoas com deficiência (PCD). Uma vez que seu funcionamento depende de mecanismos robustos de cooperação e pactuação entre os entes federados, este artigo analisa a dinâmica da Comissão Intergestores Bipartite (CIB) de São Paulo na condução da implementação da RCPD. Realizou-se uma análise documental das atas da CIB-SP de 2011 a 2019. O referencial teórico se pautou na análise de políticas públicas, utilizando abordagem multidimensional a partir das dimensões política, estrutura e organização. Na dimensão política, as pautas centrais são referentes à responsabilidade dos entes federados e demandas originárias do Ministério da Saúde e Ministério Público. A dimensão estrutura ocorre prioritariamente por pautas protocolares de informes de credenciamento/descredenciamento. Já na dimensão organização, foram classificadas como centrais: avaliação dos serviços; necessidades populacionais; oferta, fluxos, regulação assistencial e dispensação de órteses, próteses e meios auxiliares. Conclui-se que, quando não induzida por atores externos, a discussão é protocolar, reduzida aos informes de credenciamento de ações e serviços e adquire centralidade com demandas de órgãos externos e com o surgimento de novos problemas de saúde pública.

Abstract The Care Network for People with Disabilities (RCPD) was implemented in the Brazilian National Health System (SUS) to expand the access to services to people with disabilities (PWD). Since its functioning depends on robust cooperation and pact mechanisms between federated states, this article analyzes the dynamic of the Bipartite Inter-manager Commission (CIB) of São Paulo in implementing RCPD. Document analysis of the records of the CIB-SP from 2011 to 2019 was carried out. The theoretical referential was based on the analysis of public policies, using a multidimensional approach from the political, structural, and organizational dimensions. In the political dimension, the main rulings relate to the responsibilities of federated states and demands from the Ministry of Health and Public Ministry. The structural dimension comprises mainly protocol rulings regarding accreditation/de-accreditation. In the organizational dimension, at last, were classified as central: service evaluation; populational needs; offer, flow, regulation of assistance and dispensing of orthotics, prostheses, and auxiliary means. In conclusion, when it is not conducted by external actors, the discussion follows protocol, being reduced to accreditation informs of actions and services and gains centrality with demands from external organs and the emergence of new public health problems.

Mental Health Profiles of University Students and Associated Life Habits / Perfis de Saúde Mental de Estudantes Universitários e Hábitos de Vida Associados

Abstract We sought to investigate the mental health profile of university students and possible individual aspects, life habits and associated academic experiences. 844 students were included, predominantly female with a mean age of 22.57 years, who answered a socioeconomic and life habits questionnaire and the Depression, Anxiety and Stress Scale. Cluster and multinomial logistic regression analyses were performed. Three profiles were identified: students with good, moderate and poor mental health. Married or single students, from exact sciences, who studied in a public university and did not work, with low alcohol consumption were more likely to have a good mental health. Understanding the association of life habits and academic experiences with different profiles is relevant to develop interventional strategies with this public.

Resumo Buscou-se investigar os perfis de saúde mental de universitários e possíveis aspectos individuais, hábitos de vida e vivências acadêmicas associados. Participaram 844 estudantes, com predominância feminina e idade média de 22,57 anos, que responderam a Depression, Anxiety and Stress Scale e questionário socioeconômico e de hábitos de vida. Foram feitas análises de cluster e de regressão logística multinomial. Foram identificados 3 perfis: universitários com saúde mental prejudicada, mediana e boa. Estudantes solteiros ou casados, que não trabalhavam e cursavam universidade pública, curso de exatas e bebiam menos tiveram maiores chances de integrar o perfil com boa saúde mental. Compreender os hábitos de vida e vivências acadêmicas associados aos diferentes perfis é relevante para desenvolver estratégias interventivas com este público.

Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes.

Introduction: Gene therapy is a promising approach to be applied in cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies. However, cardiomyocytes are crucial cell types that are considered hard-to-transfect. The entrapment of nucleic acids in non-viral vectors, such as lipid nanoparticles (LNPs), is an attractive approach for safe and effective delivery. Methods: Here, a mini-library of engineered LNPs was developed for pDNA delivery in cardiomyocytes. LNPs were characterized and screened for pDNA delivery in cardiomyocytes and identified a lead LNP formulation with enhanced transfection efficiency. Results: By varying lipid molar ratios, the LNP formulation was optimized to deliver pDNA in cardiomyocytes with enhanced gene expression in vitro and in vivo, with negligible toxicity. In vitro, our lead LNP was able to reach a gene expression greater than 80%. The in vivo treatment with lead LNPs induced a twofold increase in GFP expression in heart tissue compared to control. In addition, levels of circulating myeloid cells and inflammatory cytokines remained without significant changes in the heart after LNP treatment. It was also demonstrated that cardiac cell function was not affected after LNP treatment. Conclusion: Collectively, our results highlight the potential of LNPs as an efficient delivery vector for pDNA to cardiomyocytes. This study suggests that LNPs hold promise to improve gene therapy for treatment of cardiovascular disease.

H2S donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma.

Introduction: Hydrogen sulfide (H2S) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation. Objectives: We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties. Methods: All the molecules are characterized for their ability to release H2S both via amperometric approach and using a fluorescent probe. The chemical stability of the newly synthesized hybrid molecules has been investigated at differing pH values and in human serum. Results: Prednisone-TBZ hybrid (compound 7) was selected for further evaluations. The obtained results from the in vitro and in vivo studies clearly show evidence in favor of the anti-inflammatory properties of the released H2S. Conclusions: The protective effect on airway remodeling makes the hybrid Prednisone-TBZ (compound 7) as a promising therapeutic option in reducing allergic asthma symptoms and exacerbations.

Older people's pleasant events and subjective well being / Prática de atividades prazerosas e bem-estar subjetivo em idosos

This study aimed to investigate the prevalence and relationships between subjective well being and involvement in pleasant events in a sample of 156 community-dwelling older people without cognitive impairment. The Brazilian version of The California Older Person's Pleasant Events Schedule assessed the involvement in pleasant events, and subjective well-being was assessed by the Life Satisfaction Scale and the Positive and Negative Affect Scale. The sample showed higher levels of positive affect compared to negative affect, higher frequency of Contemplative activities and lower frequency of Intellectual activities. Significant relationships were observed between the constructs in general, suggesting that the higher the Involvement of older people in Pleasant Events the higher their Subjective Well Being. Social and Competence activities as well as Contemplative activities showed stronger associations with Subjective Well Being. These findings are relevant for the development of interventions and public policies focused on older people's mental health.

Este estudo objetivou investigar prevalência e relações entre Bem-estar Subjetivo e Prática de Atividades Prazerosas em 156 idosos da comunidade sem comprometimento cognitivo. Foram utilizadas a versão brasileira adaptada do California Older Person's Pleasant Events Schedule para avaliar prática de atividades prazerosas, a Escala de Satisfação com a Vida e a Escala de Afetos Positivos e Negativos. A amostra apresentou média superior para afetos positivos do que negativos, maior frequência nas atividades contemplativas e menor frequência nas atividades intelectuais. Foram observadas relações significativas entre os constructos, indicando que quanto mais idosos praticam atividades prazerosas, mais experimentam Bem-estar Subjetivo. As atividades sociais e de competência e as contemplativas foram as que mais se associaram ao Bem-estar Subjetivo. Esses achados são relevantes para a elaboração de intervenções e de políticas públicas voltadas à saúde mental de idosos.

Brazilian Loneliness Scale: evidence of validity based on relations to depression, anxiety and stress / Escala Brasileira de Solidão: evidência de validade baseada na relação entre depressão, ansiedade e estresse / Escala Brasileña de Soledad: evidencia de validez baseada en la relación entre depression, ansiedad y estrés

This paper aimed mainly to investigate the relationships between Brazilian Loneliness Scale (UCLA-BR) and the levels of depression, anxiety and stress in Brazilian college students. These concepts were assessed using validated scales (Patient Health Questionnaire - PHQ-9, Depression, Anxiety and Stress Scale - DASS-21, Beck Anxiety Inventory - BAI and Lipp Stress Symptom Inventory - ISSL). A total of 325 college students participated and responded all the instruments. Descriptive, correlational and group differences analyzes were conducted. The prevalence of depression, anxiety and stress varied depending on the instrument used. UCLA-BR presented evidence of validity based on relationships with depression, anxiety and stress, especially depression (assessed by DASS-21). Analysis of measurement scales can help to understand aspects of college students' mental health. (AU)

Esse trabalho teve por objetivo principal investigar as relações existentes entre a Escala Brasileira de Solidão (UCLA-BR) e os níveis de depressão, ansiedade e estresse em estudantes universitários brasileiros. Esses conceitos foram avaliados utilizando escalas validadas (Questionário sobre a saúde do paciente - PHQ-9, Depression, Anxiety and Stress Scale - DASS-21, Inventário Beck de Ansiedade - BAI e Inventário de Sintomas de Stress de Lipp - ISSL). Participaram 325 universitários, que responderam todos os instrumentos. Foram conduzidas análises descritivas, correlacionais e de diferenças de grupo. A prevalência de depressão, ansiedade e estresse variou dependendo do instrumento utilizado. A UCLA-BR apresentou evidências de validade baseadas nas relações com depressão, ansiedade e estresse, principalmente depressão (avaliada pela DASS-21). Analisar as escalas de medida pode ajudar a compreender aspectos da saúde mental dos universitários. (AU)

Este estudio tuvo como objetivo principal investigar la relación entre la Escala Brasileña de Soledad (UCLA-BR) y los niveles de depresión, ansiedad y estrés en estudiantes universitarios brasileños. Estos conceptos se evaluaron mediante escalas validadas (Cuestionario de Salud del Paciente - PHQ-9, Escala de Depresión, Ansiedad y Estrés - DASS-21, Inventario de Ansiedad de Beck - BAI e Inventario de Síntomas de Estrés de Lipp - ISSL). Participaron 325 estudiantes, quienes respondieron a todos los instrumentos. Se realizaron análisis descriptivos, correlacionales y de diferencias grupales. La prevalencia de depresión, ansiedad y estrés varió de acuerdo con el instrumento utilizado. UCLA-BR presentó evidencias de validez basadas en relaciones con depresión, ansiedad y estrés, especialmente depresión (evaluado por DASS-21). El análisis de escalas de medición puede ayudar a comprender aspectos de la salud mental de los estudiantes universitarios. (AU)

Gender Differences in Mental Health and Beliefs about Covid-19 among Elderly Internet Users / Saúde Mental e Crenças sobre Covid-19 em Idosas e Idosos Usuários da Internet / Salud Mental y Creencias sobre Covid-19 en Ancianos y Ancianas Usuarios de Internet

Abstract Older people's mental health is at risk during the Covid-19 pandemic. This study investigated gender differences in home isolation, beliefs about Covid-19 and mental health indicators among elderly internet users during the pandemic. A total of 384 older persons (66.9% women and 30.1% men) answered an online survey devised to collect information on sociodemographic characteristics, beliefs/attitudes about Covid-19, depression (PHQ-2), loneliness (short version of the UCLA-BR), social support and resilience (the BRS). Older women showed poorer mental health indicators, were more likely to adhere to home isolation and believe in the effectiveness of this measure, and felt more self-confident to self-isolate at home. Stronger perceived vulnerability to Covid-19 and awareness of the gravity of the disease were related to poorer mental health indicators among women. Older women are a high-risk group for negative mental health outcomes during the pandemic and should therefore be a primary focus of actions to mitigate the effects of the pandemic on mental health.

Resumo A saúde mental de idosos encontra-se em risco durante pandemia de Covid-19. Este estudo teve como objetivo analisar diferenças de sexo com relação ao isolamento domiciliar, crenças sobre Covid-19 e indicadores de saúde mental em idosos usuários de internet durante a pandemia. A amostra foi composta por 384 idosos (66,9% mulheres e 30,1% homens) que responderam instrumentos online para aferir: dados sociodemográficos, crenças/atitudes sobre Covid-19, depressão (PHQ-2), solidão (versão curta da UCLA-BR), suporte social e resiliência (EBR). Idosas apresentaram piores índices de saúde mental, aderiram mais ao isolamento domiciliar, relataram acreditar mais na efetividade do isolamento e sentiram-se mais autoconfiantes em praticá-lo. Percepções mais fortes sobre vulnerabilidade e gravidade da doença apresentaram relações com piores índices de saúde mental para as idosas. Idosas compreendem grupo de risco para desfechos negativos em saúde mental na pandemia da Covid-19, devendo esse grupo ser foco prioritário para ações de mitigação dos efeitos da pandemia no âmbito da saúde mental.

Resumen La salud mental de los ancianos está en riesgo en la pandemia de la Covid-19. Este estudio tuvo como objetivo analizar las diferencias de género en relación con el aislamiento domiciliario, las creencias sobre el Covid-19 y los indicadores de salud mental en los ancianos, que son usuarios de Internet, durante la pandemia. Una muestra de 384 ancianos (66,9% mujeres y 30,1% hombres) respondieron cuestionarios online para medir: datos sociodemográficos, creencias y actitudes sobre Covid-19, depresión (PHQ-2), soledad (versión corta del UCLA-BR), apoyo social y resiliência (EBR). Las mujeres de edad avanzada presentaron los peores índices de salud mental, se adhirieron más al aislamiento en el hogar, informaron que creían más en la efectividad del aislamiento y se sentían más seguras de sí mismas al practicarlo. Las percepciones más fuertes de vulnerabilidad y gravedad de la enfermedad mostraron más relaciones significativas con los peores índices de salud mental para las ancianas. Las ancianas son un grupo de riesgo de resultados negativos para la salud mental en la pandemia de la Covid-19, y este grupo debería ser un enfoque prioritario para las acciones de mitigación de los efectos de la pandemia en la salud mental.

Relationship between loneliness and mental health indicators in the elderly during the COVID-19 pandemic / Relação entre solidão e indicadores de saúde mental em idosos durante a pandemia da COVID-19 / Relación entre la soledad y los indicadores de salud mental en ancianos durante la pandemia COVID-19

Social isolation due to the global pandemic influenced not only the way how people interact, but it also brought a huge impact on the population's mental health, regardless of their age. This study aimed to evaluate the intensity of symptoms of depression and anxiety, perceived stress, levels of loneliness, and psychological well-being in the elderly during social distancing due to the COVID-19 pandemic. The study included 86 elderlies, aged 60 to 90 years old (M=70.95; SD=7.08), living in the southern region of the country. They were interviewed by a WhatsApp video call and responded about symptoms of stress, anxiety, loneliness, depression, and positive mental health. The results showed that 55.8% had high stress symptoms, 18.6% anxiety symptoms, 16.3% depression symptoms, and 5.82% moderate to severe loneliness. It was found that participants who felt more alone had lower well-being scores (AU).

O isolamento social causado pela pandemia mundial interferiu não somente na forma como as pessoas se relacionam, mas também trouxe grande impacto na saúde mental da população, independentemente da idade. Este estudo teve como principal objetivo avaliar a intensidade de sintomas de depressão e de ansiedade, estresse percebido, níveis de solidão e de bem-estar psicológico em idosos durante o distanciamento social devido à pandemia da COVID-19. Participaram do estudo 86 idosos, de 60 a 90 anos de idade (M = 70,95; DP = 7,08), moradores da região sul do país. Eles foram entrevistados por uma chamada de vídeo por WhatsApp e responderam sobre sintomas de estresse, ansiedade, solidão, depressão e saúde mental positiva. Os resultados mostraram que 55,8% apresentaram sintomas acentuados de estresse, 18,6% sintomas de ansiedade, 16,3% sintomas de depressão e 5,82% solidão moderada a grave. Verificou-se que os participantes que se sentiam mais sozinhos apresentaram menores escores de bem-estar (AU).

El aislamiento social causado por la pandemia mundial ha interferido en la manera en que las personas se relacionan, teniendo un gran impacto en la salud mental de la población, independientemente de su edad. Este estudio tuvo como objetivo evaluar la intensidad de los síntomas de depresión y ansiedad, estrés percibido, niveles de soledad y bienestar psicológico en ancianos durante el distanciamiento social por la pandemia de COVID-19. El estudio incluyó a 86 personas mayores, de 60 a 90 años (M=70,95; DS=7,08), residentes en la región sur del país. Fueron entrevistados por una videollamada de WhatsApp y respondieron sobre síntomas de estrés, ansiedad, soledad, depresión y salud mental positiva. Los resultados mostraron que 55,8% tenía síntomas de estrés severo, 18,6% síntomas de ansiedad, 16,3% síntomas de depresión y 5,82% soledad moderada a severa. Se averiguó que los participantes que se sentían más solos tenían puntuaciones de bienestar más bajas (AU).

Indicadores de saúde mental em idosos frequentadores de grupos de convivência / Mental health indicators of the elderly from social groups / Indicadores de salud mental en ancianos que frecuentan grupos sociales

Este estudo descritivo exploratório investigou a prevalência de Prática de Atividades Prazerosas (PAP), bem-estar Subjetivo (BES), Depressão e Solidão em 59 idosos provenientes de grupos de convivência. Foram aplicados: Questionário Sociodemográfico, Escal a de Atividades Instrumentais da Vida Diária de Pfeffer, Escala de Afetos Negativos e Positivos, Escala de Satisfação com a Vida, Escala de Depressão Geriátrica - versão reduzida, Escala Brasileira de Solidão e OPPES-BR. Os idosos da amostra eram majoritar iamente mulheres, jovens idosos, viúvos, escolarizados, com bom estado funcional e que avaliavam sua saúde de forma positiva. A amostra apresentou médias altas para PAP e BES e médias baixas para solidão e depressão. Grupos de convivência favorecem a saúde mental de idosos e contribuem para o envelhecimento bem-sucedido, uma vez que esses espaços fornecem oportunidades de suporte social, engajamento em atividades prazerosas e experiência de sentimentos positivos.

This descriptive and exploratory study investigated the prevalence of Involvement in Pleasant Events, Subjective Well-Being, Depression, and Loneliness in 59 elderly from social groups without apparent cognitive impairment. A sociodemographic questionnaire, the Pfeffer Index, the Negative and Positive Affect Scale, the Life Satisfaction Scale, the Geriatric Depression Scale - reduced version, the Brazilian Loneliness Scale, and OPPES-BR were applied. The elderly were mostly women, young, widowed, educated, with a good functional state, and with a positive health evaluation. Participants showed high levels of Involvement in Pleasant Events and Subjective Well Being, and low levels of loneliness and depression. Social groups provide opportunities for social support, engagement in pleasant events, positive emotions and may contribute to the elderly's mental health and successful aging.

Este estudio exploratorio descriptivo investigó la prevalencia de la práctica de actividad placentera (PAP), el bienestar subjetivo (BES), la depresión y la soledad en 59 personas mayores proveniente de grupos sociales. Se aplicaron el Cuestionario sociodemográfico, la Escala de actividades instrumentales de la vida diaria de Pfeffer, la Escala de afectos negativos y positivos, la Escala de satisfacción con la vida, la Escala de depresión geriátrica - versión reducida, la Escala de soledad brasileña y OPPES-BR. Los ancianos de la muestra eran en su mayoría mujeres, ancianos más jóvenes, viudos, escolarizados, con buen estado funcional y que evaluaron positivamente su salud. En general, los ancianos tenían altas tasas de PAP y BES y bajas tasas de soledad y depresión. Los grupos sociales favorecen la salud mental de las personas mayores y contribuyen al envejecimiento exitoso, ya que estos espacios traen oportunidades de apoyo social, participación en actividades placenteras y experiencia de sentimientos positivos.

O mercado de trabalho para idosos: a consultoria como possibilidade de atuação / The labor market for the elderly: possibilities to work as a consultant / El mercado laboral para las personas mayores: la consultoría como posibilidad de actuación

Prestar serviços de consultoria em empresas pode ser uma alternativa para idosos que desejam permanecer ativos no mercado de trabalho. Este estudo qualitativo e exploratório tem por objetivo compreender certas percepções e atitudes atribuídas pelo idoso em seu processo laboral como consultor em empresas. Participaram desta investigação oito idosos consultores que atuavam em empresas de grande porte, selecionados por meio da técnica metodológica qualitativa intitulada "bola-de-neve". Foi elaborado e aplicado um roteiro de entrevista semi-estruturada. Os resultados foram analisados a partir da análise temática e interpretados por teorias psicológicas a partir da percepção de desenvolvimento do idoso. Evidencia-se que muitos idosos permanecem trabalhando por se identificarem com a atividade e levarem em consideração as motivações financeiras para seguir na atuação laboral. A consultoria apresenta desafios como qualquer profissão, sendo uma opção viável para alguns idosos se manterem no mercado de trabalho. No entanto, este cargo só está disponível para uma parcela específica de idosos. Outras opções de inserção no mercado de trabalho e seus impactos no bem estar precisam ainda ser investigadas.

Providing consulting services in companies can be an alternative for seniors who wish to remain active in the job market. This qualitative and exploratory study aimed to understand elderly people's perceptions and attitudes regarding their work as a consultant in enterprises. Participants were composed of eight elderly people who worked as consultants in large companies, selected for the study through the "snowball" technique. A semi-structured interview script was elaborated and applied. The results were analyzed according to thematic analysis and interpreted by psychological theories of elderly development. Older people remain working due to self identification with the activity and financial motivations. Working as a consultant brings challenges like any other job, but is a feasible option for some seniors who want to stay in the labor market. However, this position is not available for all elderly people. Other options of remaining in the labor market and their impacts on well-being still need to be investigated.

Proporcionar servicios de consultoría en las empresas puede ser una alternativa para las personas mayores que desean mantenerse activas en el mercado laboral. Este estudio cualitativo y exploratorio tiene como objetivo comprender ciertas percepciones y actitudes atribuidas por los adultos mayores en sus procesos laborales como consultor en empresas. Participaran de esta investigación ocho consultores mayores que trabajaban en grandes empresas, seleccionados por medio de la técnica metodológica intitulada "bola de nieve". Fue elaborado y aplicado un guión de entrevista semiestructurada. Los resultados fueron analizados a partir del análisis temático e interpretado por teorías psicológicas a través de la percepción del desarrollo de los ancianos. Es evidente que muchas personas mayores siguen trabajando debido a la identificación que tienen con las actividades involucradas en sus trabajos y llevaren en consideración las motivaciones financieras. La consultoría presenta desafíos como cualquier profesión y es una opción viable para algunos adultos mayores para permanecer en el mercado laboral. Sin embargo, esta posición solo está disponible para una parte específica de los ancianos. Todavía hay que investigar otras opciones de inserción en el mercado de trabajo y sus impactos en el bien estar de trabajador.

Perfis de idosos praticantes de atividades prazerosas: características sociodemográficas, vulnerabilidade social e funcionalidade / Profiles of older people who practice pleasant events: sociodemographic aspects, social vulnerability and functionality / Perfiles de ancianos practicantes de actividades placenteras: características sociodemográficas, vulnerabilidad social y funcionalidad

Este estudo mapeou perfis de idosos praticantes de atividades prazerosas e relacionou tais perfis com variáveis sociodemográficas e estado funcional. Idosos (n=330) sem comprometimento cognitivo, residentes da comunidade e com diferentes níveis de vulnerabilidade social (acessado pelo Índice Paulista de Vulnerabilidade Social) responderam um questionário sociodemográfico, a escala de Pfeffer (funcionalidade) e o OPPES-BR (prática de atividades prazerosas). Por meio da análise de cluster combinando-se o método hierárquico e não-hierárquico foram identificados cinco perfis de idosos: muito ativos; muito ativos sociáveis; minimalistas; pouco ativos contemplativos; e pouco ativos intelectuais. Manter alta frequência em diversos tipos de atividades prazerosas associou-se à maior escolaridade, menor vulnerabilidade social e menor dependência funcional. O perfil dos pouco ativos contemplativos foi o mais vulnerável, com maior declínio funcional, vulnerabilidade social e taxa de analfabetismo. Diante da diversidade de perfis de idosos, são necessárias políticas públicas favorecedoras ao acesso a atividades prazerosas, principalmente aos mais vulneráveis. (AU)

This study mapped profiles of older adults who participated in pleasant events, and related these profiles with sociodemographic and functional state. Older adults (n=330) without cognitive impairments, community residents and with different social vulnerability levels (accessed by the Paulista Index of Social Vulnerability) answered a sociodemographic questionnaire, the Pfeffer Scale (functionality) and the OPPES-BR (involvement in pleasant activities). By applying a cluster analysis, which combined the hierarchical and non-hierarchical method, five profiles of older adults were identified: highly active; highly socially active; minimalists; little active contemplative; and little active intellectual. Maintaining high frequency in pleasant activities was associated with a higher education, lower social vulnerability, and less functional dependence. The little active contemplative was the most vulnerable profile, with higher scores on functional decline, social vulnerability, and illiteracy rates. Considering the diversity of the older adult's profiles, public policies favoring the access to pleasant events are needed, especially for the most vulnerable ones. (AU)

Este estudio diseñó perfiles de ancianos que practican actividades placenteras y relacionó estos perfiles con variables sociodemográficas y estado funcional. Los ancianos (n = 330) sin comprometimiento cognitivo, residentes de la comunidad y con diferentes niveles de vulnerabilidad social (accesado por el Índice Paulista de Vulnerabilidad Social) respondieron un cuestionario sociodemográfico, Escala de Pfeffer (funcionalidad) y el OPPES-BR (práctica de actividades placenteras). Por medio de análisis de Cluster, combinando el método jerárquico y no-jerárquico, fueron identificados cinco perfiles de ancianos: muy activos; muy activos sociables; minimalistas; poco activos contemplativos; y poco activos intelectuales. Mantener alta frecuencia en diversas actividades placenteras presentó una asociación con mayor escolaridad, menor vulnerabilidad social y menor dependencia funcional. El perfil de los poco activos contemplativos fue el más vulnerable, con mayor declive funcional, vulnerabilidad social y tasa de analfabetismo. Ante la diversidad de perfiles de ancianos, son necesarias políticas públicas que favorezcan el acceso a actividades placenteras, principalmente a los más vulnerables. (AU)

Hydrogen sulfide inhibits apoptosis and protects the bronchial epithelium in an allergic inflammation mice model.

Studies suggest that hydrogen sulfide (H2S) plays a relevant and beneficial role in the pathophysiology of pulmonary allergic diseases, such as asthma. These diseases may be triggered by changes in airway epithelium caused by repeated exposure to environmental allergens. This study aimed to investigate whether H2S protects against bronchial epithelium apoptosis in allergic inflammation in mice. The effects of H2S on the production of Th2 cytokines and on the infiltration of pulmonary inflammatory cells were also studied. Female BALB/c mice previously sensitized with ovalbumin (OVA) were treated with H2S donor (sodium hydrosulfide [NaHS]) 30 min prior to OVA challenge. After euthanasia (48 h post challenge), the right lung was homogenized to study apoptosis protein expression and to analyze cytokine levels in lung tissue. The left lobe was fixed in formalin for morphological analysis of lung tissue and verification of apoptosis in situ by the TUNEL assay. Histological results showed that NaHS reduced the airway inflammatory infiltrate and prevented an increase in the IL-4, IL-5 and IL-25 levels caused by OVA challenge. Activation of caspase 3 and FasL in response to the allergen was also fully prevented by NaHS treatment. TUNEL staining showed that the challenge from OVA significantly increased the rate of apoptosis in the bronchiolar epithelium, and that this incremental apoptosis was abolished by NaHS treatment. In conclusion, our results showed that H2S donor has a protective effect against airway epithelium damage caused by an allergic reaction, and represents a potential agent in treating allergic lung disorders, such as asthma.

H2S in periodontal immuneinflammatory response and bone loss: a study in rats.

Halitosis is highly prevalent in periodontitis and attributed mainly to the presence of volatile sulfur compounds (VSC), where hydrogen sulfide (H2S) is the chief culprit in the characteristic malodor of periodontitis and thus may play an active role in its pathogenesis. The aim of this study was to evaluate the effect of H2S in the acute, intermediate and chronic immuneinflammatory host response and alveolar bone loss in vivo by using an animal model of induced periodontal disease. Thirtysix rats were divided into 2 groups: test group (n = 18), rats exposed to H2S (NaHS H2S donor molecule) and control group (n = 18), rats treated with saline only (Ctrl). All animals had one of their lower second molars ligated to induce periodontal disease (PD). The sound contralateral molar was used as control (H). Each group was subdivided into 3 (n = 6), according to followup time (3h, 5 days and 14 days). The gingival tissue was used for mRNA expression analysis (IL1, IL6, RANKL, OPG and SOFAT) by realtime PCR and the mandibles were analyzed morphometrically. Data analysis showed that the ligature promoted alveolar bone loss, observed mainly at 14 days, both in the group exposed to H2S and in the Ctrl group. H2S administration did not result in additional bone loss. Gene expression showed a significant increase in IL1, IL6, RANKL and SOFAT only in the CtrlPD group (p<0.05). A significant downregulation in OPG expression was observed over time in the CtrlPD group (p<0.05). In conclusion, H2S had no effect on alveolar bone loss in the absence of a ligature. In the presence of a ligature, however, exposure to H2S had an immunoregulatory effect on the expression of proinflammatory and proresorptive cytokines.

A halitose é altamente prevalente na periodontite e é atribuída principalmente à presença de compostos sulforosos voláteis (CSV), sendo o sulfeto de hidrogênio (H2S) o principal gás relacionado ao mau odor e que pode estar envolvido na patogênese da doença periodontal. O objetivo deste estudo foi avaliar o efeito agudo, intermediário e crônico do H2S na resposta imunoinflamatória e na perda óssea alveolar em ratos, com e sem doença periodontal induzida. Trinta e seis ratos foram divididos em 2 grupos: teste (n = 18), ratos expostos ao H2S (NaHS molécula doadora de H2S) e grupo controle (n = 18), ratos tratados apenas com solução salina (Ctrl). Todos os animais tiveram um dos seus segundos molares inferiores submetidos à colocação de uma ligadura para o desenvolvimento da doença periodontal (DP), em comparação com o dente contralateral saudável (H). Cada grupo foi subdividido em 3 (n = 6), de acordo com o tempo de eutanásia (3h, 5 dias e 14 dias). Os tecidos gengivais foram utilizados para a análise da expressão gênica (IL1, IL6, RANKL, OPG e SOFAT) por PCR em tempo real e as mandíbulas foram analisadas morfometricamente. Análise dos dados demonstrou que a ligadura promoveu perda óssea alveolar, observada principalmente aos 14 dias, tanto no grupo exposto ao H2S quanto no grupo Ctrl. A administração de H2S não resultou em perda óssea adicional. A expressão gênica demonstrou aumento significativo de IL1, IL6, RANKL e SOFAT apenas no grupo CtrlPD (p <0,05). Uma significativa regulação negativa na expressão de OPG foi observada ao longo do tempo no grupo CtrlPD (p <0,05). Podese concluir que o H2S não teve efeito adicional na perda óssea alveolar, na ausência de ligadura. Entretanto, na presença de ligadura, a exposição ao H2S teve um efeito imunorregulatório na expressão de citocinas próinflamatórias e próreabsortivas.

Comparative study between school and motor performance in children aged 6 to 11 years according to teachers' perceptions / Estudo comparativo entre desempenho escolar segundo a percepção dos professores e performance motora em crianças de 6 a 11 anos / Estudio comparativo entre desempeño escolar y motor en niños de 6 hasta 11 años

Abstract Introduction: Motor skills are enlarged during schooling age, with possible relation between motor and school performance. Objective: Compare motor skills of children with good and poor school performance, according to the teacher's perception in the classroom. Method: School children aged 6 to 11 years were divided into two groups; poor school performance (PSP) and good school performance (GSP) and evaluated using the Motor Development Scale (MDS). The chronological age, general motor age and the motor quotient of each area evaluated were compared between the groups using the Mann-Whitney Test. The Chi-square test was used to associate the motor performance classification and the school performance. Results: Chronological age was similar between groups, although the general motor age was smaller in the PSP. The general motor quotient and the motor quotients in the areas of body scheme, spatial and temporal organization were significantly smaller in PSP. Most children were classified by the MDS as Low Normal or Medium Normal motor skills in both groups; however in the GSP, 27.5% of the children had a High Normal or Superior motor development and only 2.5% were classified as Very Inferior or Inferior. In the PSP, 12.5% had a Very Inferior or Inferior performance and only 6.25% had a High Normal or Superior performance (p < 0.05 - chi-square test). Conclusion: Results show a direct connection between poor school performance and motor skill difficulties, which illustrates the relation between motor and cognitive skills.

Resumo Introdução: No período de escolarização ocorre aprimoramento e ampliação das habilidades motoras, com possível relação entre desenvolvimento motor e aprendizagem escolar. Objetivo: Avaliar e comparar habilidades motoras de crianças com baixo e alto desempenho escolar, segundo percepção do professor em sala de aula. Método: Participaram escolares entre 6 e 11 anos, divididos em GBD (baixo desempenho escolar) e GAD (alto desempenho escolar), avaliados através da Escala de Desenvolvimento Motor (EDM). As médias da idade cronológica, idade motora geral e os quocientes motores de cada um dos domínios avaliados pela EDM foram comparados entre os grupos através do Teste Mann-Whitney. O Teste Qui-quadrado foi utilizado para associar a classificação do desempenho motor e o desempenho acadêmico. Resultados: A média da idade cronológica foi semelhante entre os grupos, entretanto a média da idade motora geral foi menor no GBD. O quociente motor geral, assim como os quocientes motores: esquema corporal, organização espacial, linguagem e organização temporal foram significativamente menores no GBD. Em ambos os grupos, a maioria dos escolares foram classificados pela EDM como apresentando desempenho motor Normal Baixo ou Normal Médio, entretanto, no GAD, 27,5% dos escolares apresentaram desempenho motor Normal Alto ou Superior e apenas 2,5% foram classificadas como Muito Inferior ou Inferior. No GBD, 12,5% apresentaram desempenho Muito Inferior ou Inferior e apenas 6,25% desempenho Normal Alto ou Superior (p < 0,05 - teste qui-quadrado). Conclusão: Os resultados direcionam para uma relação direta entre baixo desempenho escolar e dificuldade nas habilidades motora, ilustrando a relação entre o desempenho motor e cognitivo.

Resumen Introducción: En el período de escolarización ocurre ampliación de las habilidades motoras, con posible relación entre el desarrollo motor y el aprendizaje escolar. Objetivo: Comparar habilidades motoras de niños con bajo y alto desempeño escolar, según la percepción de los profesores. Método: Participaron escolares entre 6 y 11 años, separados en GBD (bajo desempeño escolar) y GAD (alto desempeño escolar), evaluados a través de la Escala de Desarrollo Motor (EDM). La edad cronológica, la edad motora general y los cocientes motores se compararon entre los grupos a través del Test Mann-Whitney. El Teste Qui-cuadrado fue utilizado para asociar la clasificación del desempeño motor por la EDM y el desempeño académico. Resultados: La edad cronológica fue similar entre los grupos, sin embargo la edad motora general fue menor en el GBD. El cociente motor general, así como los coeficientes motores en los dominios esquema corporal, organización espacial, lenguaje y organización temporal, fueron significativamente menores en el GBD. En ambos grupos, la mayoría de los escolares fueron clasificados como presentado desempeño motor Normal Bajo o Normal Medio, sin embargo, en el GAD, el 27,5% de los escolares presentaron desempeño motor Normal Alto o Superior y apenas el 2,5% fueron clasificadas como Muy Inferior o Inferior. En el GBD, el 12,5% presentó un rendimiento Muy Inferior o Inferior y sólo 6,25% de rendimiento Normal Alto o Superior (p < 0,05 - prueba qui-cuadrado). Conclusión: Los resultados se dirigen para una relación directa entre el bajo desempeño escolar y la dificultad en las habilidades motrices.